Anhydrous Form I 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine compound has useful central nervous system activity.
Applicants have discovered that 2-methyl-4- 4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine (olanzapine) exists in two anhydrous forms which are clearly distinguishable by X-ray powder diffractometry. Unfortunately, anhydrous Form II olanzapine is metastable and is therefore not well suited for commercial use in pharmaceutical formulations. However, surprisingly and in accordance with the invention, it has now been discovered that the second polymorph of 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine , designated as anhydrous Form I olanzapine, is stable and is therefore well adapted for commercial use in pharmaceutical formulations.
It is desirable to prepare the substantially pure anhydrous Form I crystalline 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine to assure uniformity of product. Anhydrous Form I 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine can be prepared via a convenient, efficient, and ecologically acceptable process which utilizes the lower alcohol solvates of olanzapine claimed herein.
The crystalline anhydrous Form I 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine (Form I) and process for preparing Form I are particularly important for the commercial development of the pharmaceutically active anhydrous Form I 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine
The present invention provides the desired lower alcohol solvates of olanzapine which are particularly useful for preparing the desired anhydrous Form I olanzapine.